The role of Ca2+ in the protoveratrine-induced release of gamma-aminobutyrate from rat brain slices.
1. Protoveratrine A increased the release of gamma-amino[3H]butyrate from small slices of rat cerebral cortex. This effect increased with increasing protoveratrine concentration, reaching a maximum at 100 microM. 2. Removal of Ca2+ from the superfusing medium did not change the increase in release due to 10 microM-protoveratrine; however, the Ca2+ antagonists, compound D-600, La3+, Mn2+, Mg2+ and also high Ca2+ concentration inhibited the effect of the alkaloid, as did procaine. 3. Protoveratrine A increased the uptake of 22Na+ into the slices with a similar dose-response curve to that found for gamma-aminobutyrate release. For the most part, the substances that inhibited protoveratrine-stimulated gamma-aminobutyrate release also inhibited 22Na+ uptake, although the correlation was not perfect. 4. Although extracellular Ca2+ is not required for protoveratrine-induced gamma-aminobutyrate release, an increase in Na+ influx that is susceptible to inhibition by some Ca2+ antagonists does appear to be associated with this phenomenon. However, the possibility remains that changes in the free intracellular Ca2+ concentration may be important for transmitter release induced by depolarizing veratrum alkaloids.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011343:Procaine / Q000494:pharmacology; D011526:Protoveratrines / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D014704:Veratrum Alkaloids / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002412:Cations; D011526:Protoveratrines; D014704:Veratrum Alkaloids; D005711:Gallopamil; D011343:Procaine; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D002118:Calcium